The long-term objective of this research is to understand the regulation of skin blood flow with specific emphasis on the interaction between various physiological systems in this control process. In the past these investigators have focused on the modulation of thermoregulatory control of skin blood flow by baroreceptor and osmoreceptor mediated reflexes. In the present proposal they continue these types of investigations and complement this work with an exploration of the exact nature of the link between cutaneous sympathetic nerve activity and active cutaneous vasodilation. During changes in skin sympathetic nerve activity (SSNA), measured directly by microneurography, they will characterize the effector organ responses of human skin using laser Doppler velocimetry (LDV) to assess changes in skin blood and dew-point hygrometry to assess sweating. To understand the link between SSNA and effector organ responses the investigators use intradermal microdialysis to administer specific pharmacological blocking agents. The combination of microdialysis and LDV provides an innovative and unambiguous approach to the study of control of skin blood flow. They will characterize the relationship between spontaneously occurring bursts of SSNA and coincident thermoregulatory responses (i.e. , active vasodilatation or sweating). They expect to demonstrate that bursts of SSNA are composed of vasodilator and vasoconstrictor signals. This model will be used in combination with specific receptor antagonists to describe the contribution of acetylcholine, nitric oxide, and vasoactive peptides in this thermoregulatory response. This experimental approach provides sufficient fidelity to dissect out the relative contribution of these various local factors in thermoregulatory control of skin blood flow. Finally, the investigators will examine the interaction between activation of muscle metaboreflexes and thermoregulatory control of skin blood flow. These studies should improve our understanding of the process of neurogenic cutaneous vasodilatation and its control during combined and competing demands that result in the interaction of several physiological control systems with thermoregulatory responses. These studies should provide new knowledge related to mechanisms that humans employ to resist syncope in conditions of high circulatory and thermal stress.